In patients with gastric cancer (GC), circulating microRNA-21 (miR-21) is overexpressed and may serve as a diagnostic biomarker. In the present study, it was hypothesized that the serum miR-21 expression levels were associated with prognosis in the patients with GC. The expression levels of serum miR-21 were measured using quantitative polymerase chain reaction (qPCR) assays in 103 GC patients. Survival and Cox proportional-hazards regression analyses were performed to determine the correlation between serum miR-21 expression levels and prognosis in the patients. The correlation between the serum miR-21 levels and the clinicopathological factors of the patients was also analyzed. Survival curves were not significantly different between the groups exhibiting high and low levels of serum miR-21 expression. High levels of miR-21 in the serum were associated with an increased tumor size and an advanced pT stage. These findings suggest that serum miR-21 could be exploited as a practical biomarker for monitoring tumor burden in patients with GC.